Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23656 | 71191;71192;71193 | chr2:178575166;178575165;178575164 | chr2:179439893;179439892;179439891 |
| N2AB | 22015 | 66268;66269;66270 | chr2:178575166;178575165;178575164 | chr2:179439893;179439892;179439891 |
| N2A | 21088 | 63487;63488;63489 | chr2:178575166;178575165;178575164 | chr2:179439893;179439892;179439891 |
| N2B | 14591 | 43996;43997;43998 | chr2:178575166;178575165;178575164 | chr2:179439893;179439892;179439891 |
| Novex-1 | 14716 | 44371;44372;44373 | chr2:178575166;178575165;178575164 | chr2:179439893;179439892;179439891 |
| Novex-2 | 14783 | 44572;44573;44574 | chr2:178575166;178575165;178575164 | chr2:179439893;179439892;179439891 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs368938701  |
0.028 | 1.0 | N | 0.731 | 0.505 | None | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.49E-05 | 0 |
| P/L | rs368938701 |
0.028 | 1.0 | N | 0.731 | 0.505 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/L | rs368938701 |
0.028 | 1.0 | N | 0.731 | 0.505 | None | gnomAD-4.0.0 | 2.48057E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39177E-06 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.3268 | likely_benign | 0.3551 | ambiguous | -0.598 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | N | 0.48046209 | None | None | I |
| P/C | 0.9088 | likely_pathogenic | 0.9133 | pathogenic | -0.716 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | I |
| P/D | 0.9059 | likely_pathogenic | 0.916 | pathogenic | -0.358 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| P/E | 0.8208 | likely_pathogenic | 0.8368 | pathogenic | -0.459 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | I |
| P/F | 0.9327 | likely_pathogenic | 0.9383 | pathogenic | -0.727 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| P/G | 0.7754 | likely_pathogenic | 0.801 | pathogenic | -0.75 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | I |
| P/H | 0.6733 | likely_pathogenic | 0.6887 | pathogenic | -0.268 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| P/I | 0.8349 | likely_pathogenic | 0.8488 | pathogenic | -0.343 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | I |
| P/K | 0.8116 | likely_pathogenic | 0.8214 | pathogenic | -0.568 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | I |
| P/L | 0.4472 | ambiguous | 0.4755 | ambiguous | -0.343 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | N | 0.486755967 | None | None | I |
| P/M | 0.7958 | likely_pathogenic | 0.8128 | pathogenic | -0.416 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | I |
| P/N | 0.8332 | likely_pathogenic | 0.8478 | pathogenic | -0.335 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| P/Q | 0.6212 | likely_pathogenic | 0.64 | pathogenic | -0.56 | Destabilizing | 1.0 | D | 0.753 | deleterious | N | 0.483233567 | None | None | I |
| P/R | 0.6106 | likely_pathogenic | 0.6236 | pathogenic | -0.033 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.517452587 | None | None | I |
| P/S | 0.5274 | ambiguous | 0.5559 | ambiguous | -0.714 | Destabilizing | 1.0 | D | 0.761 | deleterious | N | 0.521762328 | None | None | I |
| P/T | 0.4598 | ambiguous | 0.4938 | ambiguous | -0.709 | Destabilizing | 1.0 | D | 0.753 | deleterious | D | 0.525415922 | None | None | I |
| P/V | 0.6942 | likely_pathogenic | 0.7218 | pathogenic | -0.393 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| P/W | 0.9586 | likely_pathogenic | 0.9592 | pathogenic | -0.805 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | I |
| P/Y | 0.9156 | likely_pathogenic | 0.921 | pathogenic | -0.523 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.